title: Comparative immunogenicity of HIV-1 gp160, gp140 and gp120 expressed by live attenuated newcastle disease virus vector.
abstract: The development of a vaccine against human immunodeficiency virus-1 (HIV-1) capable of inducing broad humoral and cellular responses at both the systemic and mucosal levels will be critical for combating the global AIDS epidemic. We previously demonstrated the ability of Newcastle disease virus (NDV) as a vaccine vector to express oligomeric Env protein gp160 and induce potent humoral and mucosal immune responses. In the present study, we used NDV vaccine strain LaSota as a vector to compare the biochemical and immunogenic properties of vector-expressed gp160, gp120, and two versions of gp140 (a derivative of gp160 made by deleting the transmembrane and cytoplasmic domains), namely: gp140L, which contained the complete membrane-proximal external region (MPER), and gp140S, which lacks the distal half of MPER. We show that, similar to gp160, NDV-expressed gp140S and gp120, but not gp140L, formed higher-order oligomers that retained recognition by conformationally sensitive monoclonal antibodies. Immunization of guinea pigs by the intranasal route with rLaSota/gp140S resulted in significantly greater systemic and mucosal antibody responses compared to the other recombinants. Immunization with rLaSota/140S, rLaSota/140L rLaSota/120 resulted in mixed Th1/Th2 immune responses as compared to Th1-biased immune responses induced by rLaSota/160. Importantly, rLaSota/gp140S induced neutralizing antibody responses to homologous HIV-1 strain BaL.26 and laboratory adapted HIV-1 strain MN.3 that were stronger than those elicited by the other NDV recombinants. Additionally, rLaSota/gp140S induced greater CD4+ and CD8+ T-cell responses in mice. These studies illustrate that rLaSota/gp140S is a promising vaccine candidate to elicit potent mucosal, humoral and cellular immune responses to the HIV-1 Env protein.
authors.affiliation: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, United States of America.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Khattar
authors.forename: Sweety
authors.initials: S
authors.lastname: Samal
authors.forename: Celia C
authors.initials: CC
authors.lastname: LaBranche
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Peter L
authors.initials: PL
authors.lastname: Collins
authors.forename: Siba K
authors.initials: SK
authors.lastname: Samal
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000097:blood; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D006168:Guinea Pigs; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral; D018928:Immunity, Mucosal; D051379:Mice; D008807:Mice, Inbred BALB C; D009522:Newcastle disease virus / Q000235:genetics*; D015202:Protein Engineering; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D014613:Vaccines, Attenuated; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D011994:Recombinant Proteins; D014613:Vaccines, Attenuated; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1